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Anabolic Steroids

MacGregor Brown & Bryce Inman

Psyc 472

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History of Performance Drug Abuse

Greeks reported using certain mushrooms and plant seed to increase performance.

Romans used drugs to increase performance of horses and gladiators to increase crowd response.

Steroids first developed in the 1930’s Used by the Germans on their soldiers and animals during WW2 to make up for

a lack of nutrition. 1950’s first used for athletic purposes in Russia and Europe.

Primarily for weightlifting. Mid 1950’s it was discovered that testosterone was the driving force behind

increased athletic performance. Used in all levels of sports, in the 1972 Olympics 68% of athletes reported using

anabolic steroids. 1991 the Federal Anabolic Control Act classified steroids as a schedule 3 drug.

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Performance Enhancing Drug Statistics

3.6% of high school students abuse steroids. Risen nearly 2% in 2002, only drug other than ecstasy to show an

increase. Men that abuse steroids have a high incidence of some form

of opioid abuse. Over 3,000,000 people in the USA have reported the use of

steroids. 1997 175,000 women reported steroid use. 15% of NCAA athletes use performance enhancing drugs. 90% of athletes reported have used some form of

performance enhancing drugs during there career.

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Daily Dietary %

of Protein (RDA)

Anabolic Steroid

Use Days for 10lb muscle mass gain

400% None 225-300

400% Heavy 30-45

300% None 225-300

300% Heavy 30-45

200% None 225-300

200% Heavy 65-75

100% None 450-900

100% Heavy 450-900

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Testosterone

Produced by Leydig’s cells in testes

Responsible for secondary sex characteristics in men

Sex glands, libido, reduced body fat percentage, increased body hair are all results from elevated levels

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Estrogen/Aromatase

Estradiol (estrogen) – primary female sex hormone, controls fertility cycle in women. Estradiol is beneficial to muscle growth

Aromatase – any enzyme which removes the 19 methyl from AAS and forms 3 double bonds on the A ring.

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DHT

Through 5-alpha reductase, testosterone is converted to a hormone 4X as potent, dihydrotestosterone

DHT binds to receptors much more avidly than testosterone

5-alpha reductase is present in high amounts in tissues of the prostate, skin, scalp, liver, and central nervous system

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What are steroids?

Fat soluble molecule which contains a system of 4 rings made up of 17 carbon atoms

E.g. cholesterol, estrogen, testosterone, progesterone, cortisol, etc. Anabolic steroid (DEA) – Any hormonal substance, chemically and

pharmacologically, related to testosterone that promotes muscle growth

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Anabolic/Androgenic

Anabolic – “building”, increased skeletal muscle mass, bone density, hemoglobin, nitrogen retention and protein synthesis

Androgenic – androgens are sex hormones that can induce male traits (e.g. growth of sex organs, increased body hair, libido, skin oil, and change in voice)

Anabolic/Androgenic steroids (AAS) seek to maximize the anabolic effects while minimizing the androgenic effects. The ratio of these anabolic/androgenic effects is called the therapeutic index. Testosterone is the baseline at 1.

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Therapeutic index of common AAS

Trade Name Generic name Therapeutic Index

Androderm Testosterone 1

Deca-Durabolin Nandrolone Decanoate

11-12

Winstrol Stanazolol 5-20

Primobolan Methenolone 7-16

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Basic modifications of Testosterone

17 alpha – Remove the H with a methyl or ethyl group, producing an oral steroid

17 beta – Add carbon atoms to this position and increase solubility in lipids

Other modifications at the carbon 2,3 9, & 19 positions – slow receptor degradation, increase steroid’s affinity for binding to receptor sites, inhibit enzymatic conversion to a weaker androgen

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Do anabolic steroids work?

Most research has shown that anabolic steroids produce no effect on muscle growth. Why?

Fowler (1965) – Nibal 20mg/day Results: No increase in muscle mass (MM)

Johnson (1968) – D-bol 10mg/day. No increase in MM

Casner(1971) – Winstrol 6mg/day. No increase in MM

Hervey (1976) – D-bol 100mg/day. No increase in MM

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AAS Administration

Oral preparations – 17 methyl alklayted to survive acidic gastric secretions, short half life (e.g. dianabol, winstrol)

Injectable solutions – prepared in water or oil. Longer release times for oil. (e.g. Nandrolone Decanoate)

Patch and gel – provides steady and constant testosterone delivery (e.g. Trenbolone)

Aerosol propellant – rapid effects, very hard to detect in drug tests

Sublingual preparations – absorbed directly into blood stream so avoid digestive system, rapid effects

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Common AAS Practices

Cycle – period of time ranging from 1 to 4 months in which AAS user takes steroids

Stacking – combining 2 or more steroids

Pyramiding – a gradual buildup in dosage, and then tapering off at the end

Wk Deca(mg) D-bol

1 100 10

2 200 15

3 300 15

4 300 20

5 200 15

6 100 15

7 100 10

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Why AAS produce muscle

Activation of rRNA resulting in protein synthesis Anticatabolic effect – block action of natural

cortisone Increase free testosterone levels Stimulates activity of IGF-1 (Insulin-like growth

factor)

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Positive side effects of AAS

Enhanced muscle mass/strength Enhanced blood volume and hemoglobin

concentration Enhanced bone density and strength Hastened healing of muscular injuries Decreased body fat Increased immune response Elevated mood

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Clinical Applications

Bone metabolism conditions – osteoporosis Testosterone deficiency conditions – male

hypogonadism, andropause Cardiovascular conditions – reduces angina

pectoris, hypertension, coronary artery disease AIDS – reduces AIDS wasting

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Common AAS

Approved in U.S.-Testosterone Cypionate

-Nandrolone Decanoate

-Fluoxyymesterone

-Stanozolol

Illegal in U.S. -Testosterone enanthate

-Methandrostenolone

-Oxandrolone

-Oxymesterone

Veterinary Steroids-Equipoise (Boldenone undecyclate)-Trenbolone

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Deca Durabolin

Nandrolone decanoate - Long acting ester

Most widely used Side effects: Water

retention, endogenous test. suppression, other mild effects

Detectable for over 1 year in drug screenings

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Dianabol (methandrostenolone)

Easy to use, very effective C17 alpha alkylated Can show extreme side

effects due to its tendency to break down into 17alpha methylestradiol, a form of estrogen that is much more active in the body

Short half life (3-5 hrs.)

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Winstrol (stanozolol)

Not capable of converting into estrogen due to modifications at the 9th C position

Prepared in both oral and injectable forms

Aside from C17 methylation, relatively few side effects.

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Side Effects

Hypertension, acne, fluid retention, hypogonadism, gynecomastia, sleep disturbances, increased aggression, epistaxis (nose bleeds), withdrawal depression, prostate enlargement, heart enlargement, virilization, abnormal blood clotting, libido reduction, appetite stimulation, benign prostate enlargement

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Acne and hair loss

Acne Sebaceous glands

(responsible for oil secretion) are stimulated by androgens

Bad acne may develop on the shoulders, back, and face

Hair loss Highly androgenic

steroids that convert to DHT will aggravate balding.

DHT chokes the hair follicle, eventually killing it

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Gynecomastia

Female breast tissue resulting from high levels of estrogen

Estrogen acts upon receptors in the breast and stimulates the growth of mammary tissue

Removed only by surgery

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Stunted Growth

If taken during adolescence or before, AAS may halt growth. This occurs because they stimulate epiphyseal plates on long bones to fuse prematurely. Once fused, no growing can occur

Stunted growth caused not by AAS, but the conversion of AAS to estrogen. AAS that do not convert to estrogen will actually promote height growth

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Cardiovascular disease

AAS have a strong effect on LDL and HDL levels

HDL is the “good” cholesterol because it removes cholesterol deposits from the arteries

LDL has the opposite effect

AAS increase LDL levels and lower HDL levels.

Oral compounds much more likely to promote this adverse effect.

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Testosterone and Aggression

AAS - pronounced effects on the limbic system

AAS can act as neurotransmitters

In supraphysiologic doses, AAS can alter function of and increase the number of receptors

Can also modulate other NT in the brain

Testosterone associated with social dominance

Test. exacerbates “fight or flight” response

Studies indicate an increase in aggression in animals treated with AAS

Prison studies, situational studies

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Permanent Steroid-Induced Rage Behavior?

Animal studies show alterations to the test. receptors in the brain. They’ve also shown modifications to other receptors

The most bothersome alterations in the brain are the increase in androgen receptors and the increased binding capacity of these receptors. After cessation of AAS use, these receptors are thought to be “hungry” for elevated androgen levels. Other NT’s recognize this deficit and may remain low (similar to andropause) resulting in depression, self esteem problems, and a greater tendency to lash out

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Cancer

AAS are just a synthetic version of hormones that are already present in the body, so the stress on organs is not very high.

As such, cancer resulting from AAS is extremely rare

The only exception to this is the use of c17 alpha alkylated compounds which are liver toxic. They have been known to induce liver damage and cancer

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Sexual Dysfunction

ImpotenceMale reproductive system

depends largely on the level of androgenic hormones. Rebound effect occurs after AAS use in which no androgens are present in the body.

Testicular atrophy

Production of test. is turned off (along with spermatogenesis) resulting in a noticeable change in size of the testicles.

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Body Dysmorphia

AAS often produce addiction and body image disorders that have been labeled as

Megorexia or bigorexia Reverse anorexia Adonis complex Muscle dysmorphia

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Women and AAS

Large amounts of test. in women can produce very noticeable side effects

VirilizationWomen develop masculine

characteristics such as a deepening of the voice, changes in skin texture, acne, libido, hair loss, body hair, and enlargement of the clitoris

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AAS & the Gateway Phenomenon

After AAS, over 50% used drugs such as:• 31% estrogen receptor inhibitors• 22% HCG• 17% diuretics and/or “uppers”• 15% pain killers

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Aromatase inhibitors/Estrogen Blockers

Aromatase InhibitorsBlocks the aromatase enzyme,

preventing test. from converting to estrogen

Slows muscle growth, suppresses HDL cholesterol, prevents water retention

e.g. Arimidex (anastrozole)

Estrogen BlockersBinds to free floating estrogen

molecules, preventing estrogen from attaching to androgen receptors

May also stimulate FSH and LH endogenous test. production

e.g. Nolvadex (Tamoxifen citrate)

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Stimulation of Test. Production

HCG - used clinically to treat hypo-gonadism. Used post-cycle to stimulate endogenous test. by mimicking LH

Clomid – used clinically as a fertility aid. Acts as an estrogen antagonist, opposes negative feedback of estrogens on hypothalmus

Hypothalamus: GnRH

Pituitary: LH, FSH

Testes

Testosterone

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Insulin

Regulates glucose levels in the blood , its role in the body is to control the uptake, utilization, and storage of amino acids, carbohydrates, and fatty acids in the body.

Insulin is both anti-catabolic and anabolic because it stimulates the use and retention of nutrients in muscle cells (specifically glycogen)

Cannot be detected in drugs tests Hypoglycemia one possible outcome of use. Can also result

in immediate death, coma, or insulin dependent diabetes.

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Cutting compunds

Clenbuterol• Beta-2 sypathomimetic,

used as a bronchodilator. • Animal studies indicate

anabolic properties, but used primarily as a thermogenic compound by directly stimulating fat cells and breaking down triglycerides. Effects are temporary due to down regulation

Thyroid hormone• Used to treat thyroid

deficiency, obesity, and other metabolic disorders

• Synthetic version of T3 which stimulates thyroid gland resulting in; acceleration of cellular reactions, increase in metabolism & cardiovascular functions.

• Rebound effect

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Steroid Precursors/Prohormones

Androstenedione Androstenediol Dehydroepiandrosterone

(DHEA)

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Androstenedione

Produced by the adrenal glands 17alpha-hydroxyprogesterone & DHEA.

Once produced it is one step away from testosterone and estrogen

Missing the a hydrogen atom in the 17th position.

Processed by the liver where the hydrogen atom is added.

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Steroid Chart

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Estrogen or Testosterone?

Testosterone Androstenedione is converted into testosterone

by 17beta-hydroxysteroid dehydrogenase, which is activated by luteinizing hormone secreted by the hypothalamus and pituitary gland

Estrogen Androstenedione may also be converted to the

estrogen, by the enzyme aromatase.

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Estrogen or Testosterone?

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Androstenediol

Similar to Androstenedione Lacks a 3-keto group that enables the

conversion into estrogen A much more androgenic compound

(produces much more male based effects)

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Why Androstenediol?

Has higher conversion rates to testosterone. Doesn’t convert into estrogen. Does not convert into DHT (cause of

balding).

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DHEA

2 steps away A precursor to testosterone that is produced

in the adrenal glands. Aids in producing Androstenedione which

produces testosterone and estrogen DHEA>Andro>Testosterone/Estrogen

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Why Take a Steroid Precursor

Increase lean muscle mass? Decrease body fat? Increase strength ? Increase libido?

Only temporarily increases blood levels of testosterone, does not cause body to naturally produce testosterone.

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Negative Side Effects

Balding Acne Enlarged prostate Reduced sperm count Increased aggression Kidney & Liver damage Disrupt the menstrual cycle Decrease levels of HDL cholesterol

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Creatine

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What is Creatine?

An amino acid taken into the body through meats and animal products.

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What does Creatine do in the body?

Once ingested creatine is synthesized into phosphocreatine in the kidneys, liver, and the pancreas.

Creatine is synthesized by the three amino acids arginine, glycine, and methionine.

Once synthesized into phosphocreatine it is transported to skeletal muscles, the heart, and the brain for energy usage.

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What Does Creatine do in the Body Cont.?

Assists with the production of ATP, which is used for short term energy exertion.

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What is ATP?

Adenosine triphosphate (ATP). ATP is used during short-term high intensity

energy output.

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How Does Creatine Assist with the Production of ATP?

When ATP is broken down during exercise, energy is produced with the loss of a phosphate ion.

During high intensity exercise, ATP is constantly broken down to ADP and Phosphorous and reproduced to provide maximum energy output.

When this occurs, phosphocreatine donates one of its phosphate ions to facilitate the resynthesis of ATP.

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Results of this Process.

Reduced muscle fatigue - the rate at which ATP is broken down does not exceed the rate at which it can be resynthesized.

Decreased Lactic Acid Faster Recovery

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Side Effects

There is no pure evidence that creatine causes actual physical harm.

Possible Risks Weight gain of 1-2kgs, due to the increase of fluid stores. Increased risk for muscle cramps, and tears due to the

increased water retention Damage to kidneys. Usage may lead to cancer causes cancer. Excessive use may decrease the bodies natural ability to

produce creatine.

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How is Creatine Taken?

Powder form Pill Serum

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Typical Dosage

5g daily – regular usage 20g daily – During loading period to build up

creatine supply in the body

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Growth Hormone (GH)

A naturally occurring hormone in the body. Signaled release from the hypothalamus. Release from the pituitary gland regulated by two

hormones. Somatostatin (SS) – decreases GH output. Growth Hormone-Releasing Hormone (GHRH) – Increase GH

output. Can also be regulated by the amount of GH and Insulin Like

Growth Factor 1 (ILGF-1) that is circulated back through the body.

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GH in the Body

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Other Factors that Increase GH

Decreased blood glucose during exercise and sleep trigger the release of GH.

High protein increase small amounts GH release. Some amino acids such as L-arginine can increase

GH by decreasing the release SS from the hypothalamus.

Niacin has been shown to increase exercise induced GH release by 300- 600% (Murray, 1995).

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Theories about GH

Somatomedin hypothesis (Daughaday, 1972).

1. GH is released from the pituitary gland.

2. Travels to the liver where it is converted into ILGF.

3. ILGF enters the blood stream and stimulates muscle growth.

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Theory 2

Dual Effector Theory - Similar to the Somatomedin hypothesis except it is believed that GH alone has anabolic effects without ILGF.

Studies in mice have shown that mice injected with GH are significantly larger than those that were solely injected with ILGF.

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How does GH Cause Muscle Growth?

Once converted into ILGF, ILGF stimulates the production of, and the conversion of satellite cells into muscle cells.

Satellite cells – Cells that lie dormant around muscle tissue until stimulated by ILGF. Have the ability to replicate the genetic makeup of muscle cells.

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Side Effects

One of the most common side effects of GH abuse is acromegaly. overgrowth of bone and connective tissue which

leads to a change in physical appearance such as a protruding jaw and eyebrow bones.

Metabolic dysfunction Glucose intolerance

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How is GH Administered

Must have a prescription. IM injections. Dosage - A weekly dosage of 0.30 mg/kg of

body weight. Very expensive!

Can be over $20,000 for an annual supply of Growth Hormone.

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Beta Blockers

Medically used to: Reduce blood pressure Migraine headaches Heart arrhythmia Alcohol withdrawals Anti-anxiety

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Athletic Uses

Reduces anxiety, jitters, and slows the heart rate. Commonly used in sports that require a steady hand.

Golf Archery Bowling Pool Biathlon Rifle shooting

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Physiological Effects

1. During heightened arousal adrenaline is produced

2. Heart rate increases and blood pressure is increased

3. Beta Blockers block the beta receptor on the muscles of the heart which reduces these effects.

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Side Effects

Impotence Low Blood Pressure Insomnia Cardiac failure Poor circulation May reduce performance capacity

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Diuretics

Increase the amount of urine formation and the rate at which it is excreted.

Used in sports that require reduced weight such as: Wrestling Horse racing Bodybuilding Boxing

Also used to mask the use of other performance enhancing drugs.

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Side Effects       

Dehydration Decreased circulation of blood volume Muscle cramps Renal disorders Dizziness          Disrupted Heart rhythm

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Blood Doping/Erythropoietin

Blood Doping Adding additional blood to the system to increase

the amount of red blood cells in the system. Increased red blood cells increases the amount of

oxygen that the body can carry.Thus, increasing the performance during endurance

sports. Illegal, but hard to detect!

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Erythropoietin

A naturally occurring hormone released from the kidneys.

Causes increased production of red blood cells. Increased oxygen capacity Increased tolerance to lactic acid.

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Side Effects

Can be very dangerous Bacterial infection Induce shock Hypertension Stroke May receive the wrong blood type Increased blood viscosity

Increased workload Increased risk for blood clots Increased risk for heart attack

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Additional Performance Enhancing Drugs

GHB Enables athlete to reach deeper state when

sleeping Body produces more growth hormone

Highly abused among athletic community as a recreational drug because it produces similar intoxication to alcohol without the caloric intake and hangover.

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Additional Performance Enhancing Drugs

GHB Enables athlete to reach deeper state when

sleeping Body produces more growth hormone

Highly abused among athletic community as a recreational drug because it produces similar intoxication to alcohol without the caloric intake and hangover.